# Determining mechanisms of ovotoxicity from per- and polyfluoroalkyl substances

> **NIH VA IK2** · OMAHA VA  MEDICAL CENTER · 2024 · —

## Abstract

Candidate - The following application is intended to provide Dr. Kendra L. Clark with the technical and
professional skills necessary to transition into an independent VA research career. Dr. Clark received her PhD
in Genetics and Genomics with a focus on reproductive toxicology in December 2019 and is currently completing
her postdoctoral training focused exclusively on reproductive health research, specifically in regulation of follicle
development, cell signaling, and impacts of per- and polyfluoroalkyl substances (PFAS) on folliculogenesis. This
award will enable Dr. Clark to expand her research training and further investigate the molecular mechanisms
responsible for environmentally induced reproductive failure in both in vitro and in vivo models, impacts of in
utero exposures on offspring health, and provide the means to prevent environmentally induced reproductive
failure and preserve fertility. Environment - These goals will be accomplished under the primary mentorship of
Dr. John S. Davis, a prominent investigator in the field of ovarian biology and reproductive endocrinology, and
who serves as VA Senior Research Career Scientist. The University of Nebraska Medical Center (UNMC) is a
leading academic health and research center that is adjacent to the Omaha VA Medical Center, where strong
scientific relationships have been established to complete the proposed studies. Research - The ovary produces
the female egg, the oocyte, and hormones which are critical for reproduction and quality-of-life. The effect of a
chemical exposure on female reproductive function depends on the developmental/life stage of the exposure as
well as the level and duration of exposure. Ovotoxicants can selectively target a follicle population in the ovary,
resulting in either temporary or permanent infertility, alter ovarian function maternally, and can also impact
offspring through pregestational or in utero exposures. PFAS are a group of synthetic chemicals that are
resistant to biodegradation and are environmentally persistent. Although virtually 100% of the U.S. population
has measurable exposure to several types of PFAS, little research has been done to understand the effects of
PFAS on reproductive health. The use of aqueous film-forming foam (AFFF) and other PFAS containing
materials at military installations has significantly contributed to the contamination of surface and ground water,
leaving military bases and the communities that surround them at higher risks for PFAS exposure. The most
frequent female reproductive health diagnoses in the VA includes menstrual disorders, endometriosis,
menopausal disorders, and osteoporosis, all of which can be attributed to abnormal functioning of the ovary.
Preliminary data for this proposal demonstrate a role for the Hippo pathway and its effector YAP1 in PFAS-
induced cell proliferation in granulosa cells and follicle growth in cultured neonatal mouse ovaries. In the
research training component of this proposal, Dr....

## Key facts

- **NIH application ID:** 10805187
- **Project number:** 1IK2BX006457-01
- **Recipient organization:** OMAHA VA  MEDICAL CENTER
- **Principal Investigator:** Kendra L Clark
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10805187

## Citation

> US National Institutes of Health, RePORTER application 10805187, Determining mechanisms of ovotoxicity from per- and polyfluoroalkyl substances (1IK2BX006457-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10805187. Licensed CC0.

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